The repeated administration of antidepressant drugs have been found to produce compensatory changes in brain neuronal systems that oppose the initial response produced by the same drugs. For example, the initial response to the administration of tricyclic and monoamine oxidase inhibitor (MAOI) antidepressants is to enhance the actions of noradrenergic and serotonergic neurons. By contrast, repeated administration of the drugs reduce Beta-adrenergic receptor mediated biochemical responses due, in part, to producing a reduced number of Beta-adrenergic receptor binding sites in brain. In addition, repeated administration of monoamine oxidase inhibitors reduce the number of receptor binding sites for serotonin. However, the physiological significance of the changes in central monoamine receptors remains to be determined. The reduction in Beta-adrenergic responses has been related to the therapeutic efficacy of antidepressant drugs because this action can account for the widely-accepted latent period of 7-20 days before the appearance of clinical improvement and for the ability of antidepressants to be taken for years without loss of their clinical therapeutic actions. If these changes in monoamine receptors produce changes in central integrative processes that are related to behavior, then they should result in altering behaviors that are produced by the activation of central monoamine receptors. The goal of this project is to determine if this occurs. This will be done by examining four behaviors that are regulated by central norepinphrine or serotonin neurons following the initial and repeated administration of antidepressant drugs to rats. Specific behavior changes that emerge as a function of repeated, but not acute, antidepressant drug treatment will be examined in detail to determine whether the behavior changes are produced by a reduction in the number of central norepinephrine and/or serotonin receptors. Finally, norepinephrine or serotonin pathways in the brain and spinal cord that are involved in the behavioral actions of repeated antidepressant drug treatment will be identified.